Prevention of pancreatic islet xenograft rejection by dietary vitamin E.

Details

Serval ID
serval:BIB_CC5EDCDE4C8D
Type
Article: article from journal or magazin.
Collection
Publications
Title
Prevention of pancreatic islet xenograft rejection by dietary vitamin E.
Journal
American Journal of Pathology
Author(s)
Vajkoczy P., Lehr H.A., Hübner C., Arfors K.E., Menger M.D.
ISSN
0002-9440 (Print)
ISSN-L
0002-9440
Publication state
Published
Issued date
1997
Volume
150
Number
4
Pages
1487-1495
Language
english
Abstract
In pancreatic islet transplantation, the adhesion of activated leukocytes to endothelial cells and the loss of microvascular integrity represent the critical microcirculatory events, which promote loss of graft function due to rejection. With the view that oxygen radicals may contribute to graft rejection, we studied the effect of the antioxidant vitamin E on microvascular rejection of islet grafts. Islets were transplanted syngeneically and xenogeneically (rat) into dorsal skin-fold chambers of hamsters, which received a non-vitamin-E-supplemented laboratory chow. Treated animals with xenografts were fed with a diet supplemented with vitamin E in a low (150 mg/kg) and high (8000 mg/kg) concentration. Intravital fluorescence microscopy demonstrated complete vascularization of syngeneic grafts at day 10 after transplantation, intact islet microcirculation at day 20 with a functional capillary density of 653 +/- 6 cm-1, and only few leukocytes adherent to the endothelial lining of the islets' microvasculature (88 +/- 23 mm-2). Xenogeneic islets showed initial signs of rejection at day 6, including adhesion of leukocytes to the microvascular endothelium (610 +/- 110 mm-2) and loss of endothelial integrity. After 20 days, functional capillary density was significantly lower (173 +/- 68 cm-1) when compared with syngeneic grafts, indicating failure of graft acceptance. Supplementation of the diet with low and high concentrations of vitamin E resulted in a significant (P < 0.05) reduction of xenograft leukocyte-endothelium interaction (146 +/- 29 mm-2 and 109 +/- 42 mm-2) at day 6 after transplantation and and adequate development of functional capillary density at day 20 (478 +/- 36 cm-1 and 539 +/- 86 cm-1; P < 0.05), indicating prevention of microvascular rejection. We conclude that dietary supplementation of the lipophilic antioxidant vitamin E attenuates leukocyte-endothelial cell interactions, preserves microvascular integrity, and thus inhibits microvascular rejection in a dose-dependent fashion. Our study underscores the pivotal mediator role of reactive oxygen species in islet xenograft rejection and, furthermore, suggests that dietary vitamin E may act as an adjunct anti-rejection treatment in clinical islet transplantation.
Keywords
Animals, Cricetinae, Diet, Graft Rejection/pathology, Graft Rejection/physiopathology, Humans, Islets of Langerhans Transplantation/pathology, Mesocricetus, Neovascularization, Physiologic/drug effects, Rats, Rats, Sprague-Dawley, Transplantation, Heterologous, Vitamin E/therapeutic use
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Create date
25/11/2011 19:33
Last modification date
20/08/2019 15:47
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